Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Jan;87(1):65–70. doi: 10.1111/j.1365-2249.1992.tb06414.x

Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells transformed with the B95-8 strain is mapped to an epitope that associates with the HLA-B8 antigen.

I S Misko 1, C Schmidt 1, M Honeyman 1, T D Soszynski 1, T B Sculley 1, S R Burrows 1, D J Moss 1, K Burman 1
PMCID: PMC1554241  PMID: 1370774

Abstract

There are two types, A and B, of Epstein-Barr virus (EBV) and B95-8 represents the common type A laboratory strain. Herein, we show in a family study that paternal EBV-specific cytotoxic T lymphocytes (CTL) generated in short-term cultures following stimulation with the autologous B95-8-transformed lymphoblastoid cell line (LCL) or B cells freshly infected with the B95-8 isolate did not lyse haploidentical B95-8 LCL expressing the HLA-A1, -B8, -DR3 paternal haplotype. In contrast, the haploidentical B95-8 LCL expressing the HLA-A11, -B51, -DR7 paternal haplotype was strongly lysed. Moreover, paternal CTL generated in response to stimulation with the B95-8 LCL expressing the haploidentical HLA-A1, -B8, -DR3 paternal haplotype included an allogeneic response against the maternal haplotype but no EBV-specific response as shown by the poor lysis of the autologous LCL target cells. However, stimulation with the haploidentical HLA-A11, -B51, -DR7 paternal haplotype resulted in the generation of both an allogeneic and an EBV-specific response. CTL clones were generated from two HLA-B8+ donors in response to stimulation with the autologous type A LCL transformed with wildtype EBV. The clones were cross-reactive for an immunodominant B95-8-associated peptide epitope that interacted with the HLA-B8 allele but failed to lyse B95-8-transformed LCL targets unless the targets were pre-coated with the exogenous peptide. A CTL clone that was initially stimulated with the autologous BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA-B8+ donor, but failed to lyse the B95-8 LCL from that donor. The observed haplotype preference can be explained in terms of sequence variation between the B95-8 and the corresponding wildtype epitope. Our findings may help to clarify the role of EBV in the pathogenesis of primary Sjögren's syndrome which is closely associated with HLA-B8.

Full text

PDF
65

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bastin J., Rothbard J., Davey J., Jones I., Townsend A. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes. J Exp Med. 1987 Jun 1;165(6):1508–1523. doi: 10.1084/jem.165.6.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bejarano M. T., Masucci M. G., Morgan A., Morein B., Klein G., Klein E. Epstein-Barr virus (EBV) antigens processed and presented by B cells, B blasts, and macrophages trigger T-cell-mediated inhibition of EBV-induced B-cell transformation. J Virol. 1990 Mar;64(3):1398–1401. doi: 10.1128/jvi.64.3.1398-1401.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bennink J. R., Yewdell J. W. Murine cytotoxic T lymphocyte recognition of individual influenza virus proteins. High frequency of nonresponder MHC class I alleles. J Exp Med. 1988 Nov 1;168(5):1935–1939. doi: 10.1084/jem.168.5.1935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braciale T. J., Sweetser M. T., Morrison L. A., Kittlesen D. J., Braciale V. L. Class I major histocompatibility complex-restricted cytolytic T lymphocytes recognize a limited number of sites on the influenza hemagglutinin. Proc Natl Acad Sci U S A. 1989 Jan;86(1):277–281. doi: 10.1073/pnas.86.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burrows S. R., Misko I. S., Sculley T. B., Schmidt C., Moss D. J. An Epstein-Barr virus-specific cytotoxic T-cell epitope present on A- and B-type transformants. J Virol. 1990 Aug;64(8):3974–3976. doi: 10.1128/jvi.64.8.3974-3976.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burrows S. R., Sculley T. B., Misko I. S., Schmidt C., Moss D. J. An Epstein-Barr virus-specific cytotoxic T cell epitope in EBV nuclear antigen 3 (EBNA 3). J Exp Med. 1990 Jan 1;171(1):345–349. doi: 10.1084/jem.171.1.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dambaugh T., Hennessy K., Chamnankit L., Kieff E. U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632–7636. doi: 10.1073/pnas.81.23.7632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fox R. I., Pearson G., Vaughan J. H. Detection of Epstein-Barr virus-associated antigens and DNA in salivary gland biopsies from patients with Sjogren's syndrome. J Immunol. 1986 Nov 15;137(10):3162–3168. [PubMed] [Google Scholar]
  9. Henle G., Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. doi: 10.1128/jb.91.3.1248-1256.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Joly E., Salvato M., Whitton J. L., Oldstone M. B. Polymorphism of cytotoxic T-lymphocyte clones that recognize a defined nine-amino-acid immunodominant domain of lymphocytic choriomeningitis virus glycoprotein. J Virol. 1989 May;63(5):1845–1851. doi: 10.1128/jvi.63.5.1845-1851.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McCombs C. C., Michalski J. P., deShazo R., Bozelka B., Lane J. T. Immune abnormalities associated with HLA-B8: lymphocyte subsets and functional correlates. Clin Immunol Immunopathol. 1986 Apr;39(1):112–120. doi: 10.1016/0090-1229(86)90210-2. [DOI] [PubMed] [Google Scholar]
  12. McMichael A., McDevitt H. The association between the HLA system and disease. Prog Med Genet. 1977;2:39–100. [PubMed] [Google Scholar]
  13. Miller G., Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. doi: 10.1073/pnas.70.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Misko I. S., Moss D. J., Pope J. H. HLA antigen-related restriction of T lymphocyte cytotoxicity to Epstein-Barr virus. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4247–4250. doi: 10.1073/pnas.77.7.4247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Misko I. S., Pope J. H., Hütter R., Soszynski T. D., Kane R. G. HLA-DR-antigen-associated restriction of EBV-specific cytotoxic T-cell colonies. Int J Cancer. 1984 Feb 15;33(2):239–243. doi: 10.1002/ijc.2910330212. [DOI] [PubMed] [Google Scholar]
  16. Misko I. S., Schmidt C., Moss D. J., Burrows S. R., Sculley T. B. Cytotoxic T lymphocyte discrimination between type A Epstein-Barr virus transformants is mapped to an immunodominant epitope in EBNA 3. J Gen Virol. 1991 Feb;72(Pt 2):405–409. doi: 10.1099/0022-1317-72-2-405. [DOI] [PubMed] [Google Scholar]
  17. Misko I. S., Soszynski T. D., Kane R. G., Pope J. H. Factors influencing the human cytotoxic T cell response to autologous lymphoblastoid cell lines in vitro. Clin Immunol Immunopathol. 1984 Sep;32(3):285–297. doi: 10.1016/0090-1229(84)90273-3. [DOI] [PubMed] [Google Scholar]
  18. Moss D. J., Misko I. S., Burrows S. R., Burman K., McCarthy R., Sculley T. B. Cytotoxic T-cell clones discriminate between A- and B-type Epstein-Barr virus transformants. Nature. 1988 Feb 25;331(6158):719–721. doi: 10.1038/331719a0. [DOI] [PubMed] [Google Scholar]
  19. Moss D. J., Rickinson A. B., Pope J. H. Long-term T-cell-mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes. Int J Cancer. 1978 Dec;22(6):662–668. doi: 10.1002/ijc.2910220604. [DOI] [PubMed] [Google Scholar]
  20. Rickinson A. B., Moss D. J., Wallace L. E., Rowe M., Misko I. S., Epstein M. A., Pope J. H. Long-term T-cell-mediated immunity to Epstein-Barr virus. Cancer Res. 1981 Nov;41(11 Pt 1):4216–4221. [PubMed] [Google Scholar]
  21. Saito I., Servenius B., Compton T., Fox R. I. Detection of Epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren's syndrome. J Exp Med. 1989 Jun 1;169(6):2191–2198. doi: 10.1084/jem.169.6.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sculley T. B., Sculley D. G., Pope J. H., Bornkamm G. W., Lenoir G. M., Rickinson A. B. Epstein-Barr virus nuclear antigens 1 and 2 in Burkitt lymphoma cell lines containing either 'A'- or 'B'-type virus. Intervirology. 1988;29(2):77–85. doi: 10.1159/000150032. [DOI] [PubMed] [Google Scholar]
  23. Sixbey J. W., Shirley P., Chesney P. J., Buntin D. M., Resnick L. Detection of a second widespread strain of Epstein-Barr virus. Lancet. 1989 Sep 30;2(8666):761–765. doi: 10.1016/s0140-6736(89)90829-5. [DOI] [PubMed] [Google Scholar]
  24. Takahashi H., Merli S., Putney S. D., Houghten R., Moss B., Germain R. N., Berzofsky J. A. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science. 1989 Oct 6;246(4926):118–121. doi: 10.1126/science.2789433. [DOI] [PubMed] [Google Scholar]
  25. Venables P. J., Teo C. G., Baboonian C., Griffin B. E., Hughes R. A. Persistence of Epstein-Barr virus in salivary gland biopsies from healthy individuals and patients with Sjögren's syndrome. Clin Exp Immunol. 1989 Mar;75(3):359–364. [PMC free article] [PubMed] [Google Scholar]
  26. Whittingham S., McNeilage J., Mackay I. R. Primary Sjögren's syndrome after infectious mononucleosis. Ann Intern Med. 1985 Apr;102(4):490–493. doi: 10.7326/0003-4819-102-4-490. [DOI] [PubMed] [Google Scholar]
  27. Young L. S., Yao Q. Y., Rooney C. M., Sculley T. B., Moss D. J., Rupani H., Laux G., Bornkamm G. W., Rickinson A. B. New type B isolates of Epstein-Barr virus from Burkitt's lymphoma and from normal individuals in endemic areas. J Gen Virol. 1987 Nov;68(Pt 11):2853–2862. doi: 10.1099/0022-1317-68-11-2853. [DOI] [PubMed] [Google Scholar]
  28. Zimber U., Adldinger H. K., Lenoir G. M., Vuillaume M., Knebel-Doeberitz M. V., Laux G., Desgranges C., Wittmann P., Freese U. K., Schneider U. Geographical prevalence of two types of Epstein-Barr virus. Virology. 1986 Oct 15;154(1):56–66. doi: 10.1016/0042-6822(86)90429-0. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES